Triethylamine → [1-(5-Methylsulfanyl-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester

HRID 1040490Notes

Reaction equation

HRID 1040490 reaction equation
[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14](I)=[CH:13][N:12]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:19][S-:20].[Na+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.CCN(CC)CC>C([O-])(O)=O.[Na+].[Cl-].[Na+].O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CO.O1CCOCC1>[C:1]([O:5][C:6](=[O:18])[NH:7][C:8]1([C:11]2[CH:16]=[CH:15][C:14]([S:20][CH3:19])=[CH:13][N:12]=2)[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2]

Participants

11

Reactant 4

HCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 4378561Sodium methanethiolateHCID 58431130[1-(5-Iodo-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester

Product 1

HCID 58430866[1-(5-Methylsulfanyl-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl esterYield 77%

Reagents, catalysts & solvents 6

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolventHCID 516892Sodium BicarbonateSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
100 °C

Procedure

In a Biotage microwave vial was placed [1-(5-iodo-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester (500 mg, 1.39 mmol), sodium thiomethoxide (292 mg, 4.17 mmol) and Xantphos (80 mg, 0.14 mmol). The vial was flushed with Ar. 1,4-Dioxane (7.5 ml) and Et3N (0.48 mL, 2.78 mmol) were added. Ar was bubbled through the reaction solution for 15 minutes. Pd2(dba)3 (65 mg, 0.07 mmol) was added and the reaction was thermally heated to 100° C. After 8 h, the reaction was transferred to a separatory funnel, diluted with saturated NaHCO3 and brine, and extracted with EtOAc (2×50 mL). The combined organic layers were dried, filtered and evaporated to give a black oil. Flash chromatography (10 g silica, 0-10% MeOH in DCM) yielded 300 mg of [1-(5-methylsulfanyl-pyridin-2-yl)-cyclopropyl]-carbamic acid tert-butyl ester as a dark oil.

Workup

  1. customThe vial was flushed with Ar
  2. customAr was bubbled through the reaction solution for 15 minutes
  3. customthe reaction was transferred to a separatory funnel
  4. extractionextracted with EtOAc (2×50 mL)
  5. customThe combined organic layers were dried
  6. filtrationfiltered
  7. customevaporated
  8. customto give a black oil

Sources & evidence

ORD record
ord-278f46cd770a49a7a121e4ae0b916093
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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